FAPI-Targeted Molecular Imaging: Transforming Insights into Post-Ischemic Myocardial Remodeling?

Abstract

Post-ischemic myocardial remodeling significantly impacts clinical outcomes after acute myocardial infarction (MI), involving structural and functional changes such as ventricular dilation, infarct wall thinning, and fibrosis development. These processes, driven by inflammatory cascades, neurohormonal activation, and extracellular matrix remodeling, result in impaired cardiac output and an increased risk of heart failure. Imaging with fibroblast activation protein inhibitors (FAPI) has emerged as a promising non-invasive tool for assessing myocardial fibrosis via positron emission tomography (PET) or single-photon emission computed tomography (SPECT), targeting activated fibroblasts; the mediators of reparative and fibrotic processes. This innovative approach enables precise visualization and quantification of fibrosis dynamics, surpassing traditional imaging modalities. Preclinical studies using [⁶⁸Ga]Ga-FAPI PET/computed tomography (CT) demonstrated the tracer's specificity for fibroblast activation and its peak uptake in the infarct border zone at day 6 post-MI. These findings, corroborated by histology and autoradiography, highlight its potential for tracking reparative fibrosis. Clinical translation of FAPI imaging was recently achieved with [⁶⁸Ga]Ga-FAPI-46 PET/magnetic resonance imaging (MRI), showing persistent fibroblast activity beyond infarct zones and strong correlations with myocardial injury markers. Complementary research on [^99mTc]Tc-HFAPi SPECT imaging in patients post-MI established its predictive value for left ventricular remodeling, emphasizing its cost-effectiveness and accessibility compared with PET. These advancements underscore FAPI-based imaging's potential to transform risk stratification and therapeutic guidance in post-MI care.